The invention relates to absorbent articles such as diapers, training pants, adult incontinence briefs, feminine hygiene products and the like, that incorporate a skin care composition that comprises an enzyme inhibitor, preferably on a wearer-contacting surface. During normal wear of the article the enzyme inhibitor is transferred with the skin care composition to at least a portion of the wearer""s skin where it is available to inactivate fecal enzymes and reduce the redness and inflammation that can occur following prolonged exposure of skin to body wastes.
Diaper rash is a common form of irritation and inflammation of those parts of an infant""s body normally covered by a diaper. This condition is also referred to as diaper dermatitis, napkin dermatitis, napkin rash and nappy rash. While certainly more common in infants, this condition is not, in fact, limited to infants. Any individual who suffers from incontinence to the extent that the use of absorbent articles is required may develop this condition. Susceptible individuals range from newborns, to the elderly, to critically ill or nonambulatory individuals. 21 C.F.R. 333.503 defines diaper rash as xe2x80x9c[a]n inflammatory skin condition in the diaper area (perineum, buttocks, lower abdomen, and inner thighs) caused by one or more of the following factors: moisture, occlusion, chafing, continued contact with urine or feces or both, or mechanical or chemical irritation.xe2x80x9d It is generally accepted by the medical profession that true diaper rash or diaper dermatitis is a condition which is, in its most simple stages, a contact irritant dermatitis resulting from extended contact of the skin with urine, or feces, or both. Among the most commonly accepted factors linked to diaper rash are ammonia, fecal enzymes, bacteria, the products of bacterial action, urine pH, and Candida albicans. 
Many types of disposable absorbent products, such as diapers, training pants, adult incontinence devices, sanitary napkins, panty liners, and the like, are available that have a high capacity for absorbing urine and other body exudates. Disposable products of this type generally comprise some sort of liquid-pervious topsheet material, an absorbent core, and a liquid-impervious backsheet material. Although these types of absorbent structures may be highly efficient for the absorption of liquids, they cannot absorb bowel movements. Typically, the bowel movement is trapped between the outer surface of the fluid-permeable topsheet and the skin of the wearer, much of it adhering to the wearer""s skin. Thus the skin is exposed to contact with feces, often for long periods of time, and is susceptible to irritants present in the feces that can produce or contribute to diaper rash.
Because enzymes are widely distributed in plants, molds, bacteria, milk, milk products, and almost all animal tissues as well as in digestive juices in the gastrointestinal tract, they are almost always present in the diapered area when it has been soiled by human waste. Enzymes present in feces include proteolytic enzymes, lipases and other esterases and diesterases, ureases and other enzymes including amylases, elastases, nucleases, and the like. Although the relative contribution of the different types of enzymes to skin irritation is unknown, there is evidence that at least fecal proteolytic and lipolytic enzymes, of intestinal and/or pancreatic origin, play a direct role in causing the skin inflammation of diaper rash.
Studies with inhibitors designed to inhibit the enzymatic activity of various classes of proteases have shown that serine proteases, cysteine proteases and metalloproteases were the most likely to be responsible for the overall proteolytic activity of feces. It is known that the serine proteases trypsin and chymotrypsin, in particular, are nearly always present in grossly measurable quantities in the stools of normal young children, and smaller but detectable quantities are present in normal adult stools. Lipases, including esterases that hydrolyze dietary triglycerides, are also found in normal stools and are capable of hydrolizing triglycerides and other glycerides found in human skin to form irritating fatty acid and glycerol by-products. Thus, when skin is exposed to enzymes such as lipases and proteases present in body exudates, lipid-containing components and protein-containing components of the skin, especially of the barrier layer (stratum corneum), can be broken down resulting in the irritation and inflammation of diaper rash. Moreover, perturbation of the skin barrier allows other components of urine and feces, ammonia, bacteria and the like which may not otherwise be irritating by themselves, to migrate through the compromised skin barrier to produce additional irritation and possible infection.
It is known that bile salts are also present in body exudates. These bile salts are known normally to emulsify lipids in the body to ensure that the lipase enzymes are capable of performing at the lipid/water interface. Bile salts are also active when excreted in feces and other exudates and are available to act as coenzymes and enhance the activity of lipases that attack lipids in the stratum corneum of the skin that is exposed to body exudates.
The irritating effects of fecal enzymatic activity toward the skin are likely to be amplified if urine is present and/or if the skin is occluded. The production of ammonium hydroxide by the action of the bacterial enzyme urease on urine results in an increase in pH, for example to levels of 7.0 and above, at which the enzymatic activity of proteases and other enzymes such as lipases present in feces is enhanced. For example, the optimal pH range for urease activity is 6.4-6.9, for trypsin 7.8-8.2, and for lipases 7.5-9.5. At a pH greater than 7.0, free ammonia is released from urine as a toxic additional skin irritant. Urine itself can also contribute to diaper rash by adding moisture to the diaper environment. Water, and particularly water in the form of urine, is especially effective at diminishing the barrier property of skin, thereby enhancing the susceptibility of skin to fecal enzyme irritation. Since urine and feces are commonly present in the absorbent article at the same time, and exposure to the skin for several hours is not uncommon, suitable conditions and ample time are available for this interaction and the resulting skin damage to occur. An alkaline feces pH is a further contributing factor to enhanced enzymatic activity of feces. For example, it is well known that although the feces of breast-fed babies are usually acidic, the feces of bottle-fed and spoon-fed infants are generally alkaline, with a pH ranging from slightly alkaline (pH 7.2-7.5) to very alkaline (pH 8.7 and above). Thus, bottle-fed and spoon-fed infants in particular may have a propensity to develop diaper rash due to pH-enhanced activity of fecal enzymes.
In view of the contribution of alkaline pH to enhanced fecal enzyme activity, several attempts have been made to maintain skin pH by the use of pH control agents, such as buffering agents or weak acids, in the absorbent article or as ingredients in topically applied skin care products. It is thought that effectively maintaining skin pH in its natural acidic state (i.e., about 3.0 to about 5.5) may counteract the irritating effects of ammonia and reduce the activity of fecal enzymes. Reducing the enzymatic activity on the skin by this approach, however, is potentially difficult in the situation where feces are deposited directly on the skin following a bowel movement.
Certain anti-enzyme compounds have been included in topically applied compositions for treatment or prevention of diaper rash caused by the prolonged contact of human skin with body wastes. For example, U.S. Pat. No. 4,556,560 describes compositions containing water-soluble lipase inhibitors that are preferably metallic salts such as zinc chloride in a barrier-like carrier such as polyethylene glycol. If incorporated into a diaper topsheet or absorbent core, the lipase inhibitor is preferably in an aqueous or volatile carrier such as ethanol for transfer to the skin when the diaper is wetted with urine. U.S. Pat. No. 5,091,193 describes compositions for application to the skin at the time of diaper change that contain a chelating agent, such as phytic acid, ethylenediamine tetraacetic acid (EDTA), and the like, that restricts the availability of metals that ureases and proteases require as cofactors for activity. The composition may further include a lipase substrate such as an ester of a fatty alcohol or an additional anti-enzyme, such as a saturated or unsaturated, linear or branched, zinc salt of a fatty acid of 2 to 22 carbon atoms or an aminated acylated acid such as propionylcysteine, propionylhydroxyproline or caproylcysteine.
While compositions for the treatment of diaper rash have been described that include certain inhibitors of enzyme activity, there has been no previous description of a regimen for treatment or prevention of diaper dermatitis by which skin care compositions containing enzyme inhibitors are included in absorbent articles for automatic transfer to the skin of a wearer during normal wear of a treated article, or that the use, preferably the repeated use, of such absorbent articles automatically transfers sufficient levels of the enzyme inhibitors to selected regions of the wearer""s skin to provide a defense against fecal penetration and enzymatic activity. Moreover, there has been no previous description of absorbent articles having a skin care composition containing an enzyme inhibitor immobilized (at room temperature) on a wearer-contacting surface, preferably a topsheet, wherein the skin care composition and enzyme inhibitor are transferred to the skin of the wearer when the skin care composition is warmed to body temperature.
The invention provides an absorbent article, at least a portion of which comprises a skin care composition that comprises an enzyme inhibitor, wherein the skin care composition, including the enzyme inhibitor, is at least partially transferred from the article to the skin of a wearer of the article as a result of normal contact, wearer motion and/or body heat. The enzyme inhibitor is any material that inhibits the activity of one or more enzymes, preferably at an IC50, as measured by the General Fecal Enzymes Method defined below, of not more than about 500 micromolar (xcexcM). Suitable enzyme inhibitors for use in the article of the invention include, but are not limited to, protease inhibitors, lipase inhibitors, elastase inhibitors, urease inhibitors, amylase inhibitors, and the like, and further include inactivators of bile salts which otherwise would act as cofactors for lipase activity. The skin care composition preferably comprises about 0.001% to about 50% of the enzyme inhibitor, typically about 0.01% to about 25%, more typically about 0.1% to about 10%, and most typically about 0.1% to about 5%.
The nature of the skin care composition comprising the enzyme inhibitor may vary widely, but in one preferred embodiment is solid or semi-solid at room temperature (20xc2x0 C.). In a particularly preferred embodiment, the skin care composition will further comprise about 5% to about 95% of an emollient having a plastic or fluid consistency at 20xc2x0 C. Most preferably, the skin care composition further comprises about 5% to about 95% of an agent that is capable of immobilizing the emollient in the article and that has a melting point of at least about 35xc2x0 C. Preferably, the portion of the absorbent article incorporating the skin care composition comprising the enzyme inhibitor is a wearer-contacting surface, which is more preferably a liquid pervious topsheet.
Since the enzyme inhibitor is transferred to the skin with the skin care composition, the inhibitor is available at the skin/urine and skin/feces interfaces to inhibit enzymatic activity on the skin and reduce or prevent the occurrence of inflammation. Repeated application of similar treated articles to the wearer""s skin provides an available source with which the enzyme inhibitor transfers onto the skin continuously over time and accumulates to provide a proactive defense against harmful enzymes for the treatment and/or prevention of diaper dermatitis.